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Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15
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2018
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Homeostatic MechanismImmunologyFood IntakeHypothalamic CircuitsPhysiological RegulationGastrointestinal Peptide HormoneMetabolic SyndromeHypothalamic PeptideMetabolic SignalingAppetite ControlHealth SciencesAppetiteEnergy HomeostasisMolecular PhysiologyAppetite SuppressionImmune FunctionEndocrinologyPharmacologyNeurophysiologyBrainstem-restricted ReceptorPhysiologyNeuroscienceBrainstem Parabrachial NucleusCentral Nervous SystemMedicine
Loss of appetite, and even aversion to food, is a common experience during periods of illness (e.g. infection and pyrexia) and/or treatment (e.g. chemotherapy). This responses is distinct from the body’s homeostatic mechanisms (the hypothalamic leptin receptor-AGRP-POMC-MC4R axis), which normally regulate appetite and weight gain in children, or weight maintenance in adults. Previous work identified the brainstem parabrachial nucleus as a mediator of the appetite suppression induced by the anorectic hormones, amylin and cholecystokinin. Here, the authors identify the receptor for GDF15 (also known as macrophage-induced cytokine 1, MIC-1), a member of the TGF-beta superfamily, which shows marked increases in circulatory concentrations during various conditions of stress, illness and inflammation, and which has long been known to suppress food intake in mice. They show that its receptor, GFRAL, is expressed exclusively in the brainstem, and is undetectable in all other regions, including the hypothalamus.